This is a proposal to continue a program project directed to the comprehensive understanding of the basic derangements of cell function which lead to mental retardation in children. The underlying approach is the application of biochemical techniques to delineate the abnormalities responsible for retardation syndromes associated with inherited metabolic diseases by investigation of model systems ranging from patients and intact animals to isolated cells and subcellular systems. Emphasis will be placed on growth and development as important factors. The program project is composed of five individual research projects, each to be directed by an experienced researcher. These are 1) The use of mass spectrometry for the investigation of children with metabolic disease affecting growth and development. 2) Studies of myelin biochemistry with isolated oligodendrocytes. 3) Regulation and reactivity of lysosomal enzymes during perinatal development. 4) Regulation of galactose metabolism and galactose neurotoxicity. 5) Neuronal cells as model systems for mental dysfunction.